Bioactive Silver Nanoparticles Coated with Curcumin Inhibit Angiogenesis through MMP-9 and Cox-2 Down-Regulation

Inhibition of angiogenesis is an attractive approach in cancer therapy. Both curcumin and silver nanoparticles (AgNPs) have demonstrated anti-angiogenic properties; however, the the poor water solubility of Curcumin and the side effects of AgNPs adversely affect their activity.

In this study, AgNPs coated with curcumin (Cur-AgNPs), was used to improve aqueous-phase solubility of curcumin and decrease the side effects of AgNPs. Afterwards, treatment with curcumin enhanced the anti-angiogenic activity of Cur-AgNPs. The nanoparticles were synthesized as both reducing and stabilizing agents. Evaluation of anti-angiogenesis was assessed in vitro using Human Umbilical Vein Endothelial Cells (HUVECs) and in vivo through the Chorioallantoic Membrane (CAM) assay. Data were analyzed by one-way ANOVA with Tukey's multiple comparison test.

Synthesized Cur-AgNPs have an average diameter of 39 nm, with spherical shapes and an absorbance peak at 450 nm in the UV-visible spectrum. Cur-AgNPs showed a negative zeta potential. EDAX and FTIR confirmed the conjugation of curcumin with AgNPs. In vitro anti-angiogenesis assays demonstrated that Cur-AgNPs reduced the viability of HUVECs, an Inhibitory Concentration (IC50) value of 13 μg/ml. DAPI and acridine orange/propidium iodide staining revealed a significant increase in apoptotic cells following treatment with Cur-AgNPs. The expression of Matrix Metalloproteinase 9 (MMP-9) and Cyclooxygenase-2 (COX-2) was also inhibited in treated cells. In vivo anti-angiogenesis assays using the CAM model showed significant decrease in the number, length and hemoglobin content of CAM blood vessels.

Curcumin conjugated with AgNPs may represent a promising strategy to enhance the therapeutic potential of both AgNPs and curcumin. However, further investigations, particularly regarding safety and biocompatibility of Cur-AgNPs, is needed in this field.